Nikander, E., Metsa-Heikkila, M., Ylikorkala, O., & Tiitinen, A. (2004). Effects of phytoestrogens on bone turnover in postmenopausal women with a history of breast cancer. Journal of Clinical Endocrinology and Metabolism, 89, 1207–1212.
The study explored the effects of daily use of isoflavonoids on climacteric symptoms and QOL in postmenopausal women who had been treated for breast cancer.
Phytoestrogen tablets and similar-looking placebo tablets (six tablets per day) were taken every 12 hours with a glass of water. The participants were seen at the research center before and after each treatment period. Sixty-two postmenopausal, symptomatic women were randomized to use either phytoestrogen (tablets containing 114 mg of isoflavonoids) or a placebo for three months; the treatment regimens were reversed after a 2-month washout period.
Six women discontinued the trial for various reasons during the first phase. Thus, 56 women completed the study. The mean age pf participants was 54 (± 6 years).
This was a randomized placebo-controlled crossover trial of phytoestrogens in treatment of menopause in breast cancer participants.
At each visit, the participants were interviewed about hot flashes and other typical climacteric symptoms using the Kupperman index and Menopausal Visual Analogue scale. Blood levels of phytoestrogens, FSH, LH, estradiol, and sex hormone-binding globulin, liver enzymes, and creatinine levels were followed. Compliance with treatment was confirmed by diary records and by measurement of serum phytoestrogen levels.
The use of phytoestrogens led to significant rises in the levels of phytoestrogens, whereas the placebo regimen had no effect. Kupperman indexes at the end of treatment with phytoestrogen or placebo did not differ. Hot flashes and the other components of the Kupperman index were not relieved by the phytoestrogen regimen when evaluated separately.
Pure isoflavonoids at a dose of 114 mg for three months did not relieve hot flashes or other menopausal symptoms in participants with breast cancer
Potential limitations of the trial included:
Nightingale, C.L., Rodriguez, C., & Carnaby, G. (2013). The impact of music interventions on anxiety for adult cancer patients: A meta-analysis and systematic review. Integrative Cancer Therapies.
To clarify the effect of music interventions on anxiety for adult patients with cancer from rigorously conducted studies
TYPE OF STUDY: Meta-analysis and systematic review
Patients were undergoing active antitumor treatment.
Length of the intervention varied substantially from 5 minutes to 4 hours. There was high variability in the number of sessions delivered. Most studies examined a single intervention with immediate pre and post anxiety measurement. Three delivered live music, 1 involved a music therapist, and 11 involved listening to music via headphones. Meta-analysis showed no significant difference between the music intervention and controls (SMD = -0.003 (95% CI -0.51, 0.52).
Meta-analysis showed no significant effect of music interventions on anxiety in adults with cancer.
Results of this analysis do not support an effect of music interventions on anxiety in adults with cancer.
Nieuweboer, A.J., de Graan, A.M., Hamberg, P., Bins, S., van Soest, R.J., van Alphen, R.J., . . . Mathijssen, R.H. (2016). Effects of budesonide on cabazitaxel pharmacokinetics and cabazitaxel-induced diarrhea: A randomized, open-label multicenter phase II study. Clinical Cancer Research. Advance online publication.
To evaluate the effects of budesonide on cabazitaxel-induced diarrhea during two treatment cycles
Patients were randomized to receiver cabazitaxel plus prednisone or cabazitaxel plus prednisone with 9 mg budesonidedaily for 44 days. Budesonide was given for the first two courses and was begun two days before chemotherapy administration. Loperamide was used for diarrhea.
PHASE OF CARE: Active antitumor treatment
Among those receiving budesonide, 18% had grade 2 or 3 diarrhea, compared to 12% in the comparison group. Seven patients were hospitalized for diarrhea during treatment. No difference in diarrhea grade or prevalence existed between study groups.
Budesonide had no significant effect on the incidence or severity of diarrhea.
Budesonide was not shown to be effective to reduce the prevalence or severity of diarrhea among patients receiving cabazitaxel.
Nielsen, B.N., Aagaard, G., Henneberg, S.W., Schmiegelow, K., Hansen, S.H., & Romsing, J. (2012). Topical morphine for oral mucositis in children: Dose finding and absorption. Journal of Pain and Symptom Management, 44(1), 117–123.
To investigate the dose-response relationship of topical morphine and pain in pediatric cancer patients with oral mucositis; to investigate, after topical morphine administration, the plasma levels of morphine and metabolites
The sample included 12 children receiving treatment for chemotherapy-induced oral mucositis. Seven patients were in the dose-response study and five were in the absorption group.
Both groups received oral morphine for pain relief. All children in the study received an oral solution containing morphine hydrochloride, 1 or 2 mg/ml, administered as a spray by means of an atomizer. The child was then to retain the solution in the mouth for 10 seconds before spitting out the solution. All children in the study also received 10‐15 mg/kg acetaminophen every 6 hours. Supplemental analgesics were allowed in the study either by patient-controlled analgesia pump or intravenously.
Prospective observational sequential study
In the dose-response group, the morphine mouthwash was associated with a decrease of at least 36% in the oral pain score of six of seven patients. Thirty minutes after topical doses of 0.25–0.4 mg/kg morphine, pain decreased by approximately 36%. The absorption study reported concentrations of morphine and metabolites well below effective analgesic levels; authors reported no increase in plasma concentration of morphine.
The extremely small sample size prevents applying study results to the pediatric population of patients diagnosed with oral mucositis. Further research should investigate the reliability of these findings.
The evidence from this study is insufficient to allow researchers to draw conclusions about the effect of topical morphine on the pain associated with oral mucositis. However, oral analgesics such as morphine could be effective supplements, causing few side effects, to established treatments. More research is needed.
Nicoli, F., Constantinides, J., Ciudad, P., Sapountzis, S., Kiranantawat, K., Lazzeri, D., . . . Chen, H.C. (2015). Free lymph node flap transfer and laser-assisted liposuction: A combined technique for the treatment of moderate upper limb lymphedema. Lasers in Medical Science, 30, 1377–1385.
To determine the effectiveness of laser liposuction in combination with a lymph node flap transfer on moderate upper limb lymphedema in patients with breast cancer
Patients first received a lymph node flap transfer. The lymph node flap was placed in the wrist. Laser liposuction was scheduled one to three months following the flap procedure to debulk the affected limb. Measurements were taken preoperatively and at three and six months following the procedure.
Prospective clinical study with pre- and post-test measures
Six months after treatment, patients showed a reduction in arm circumference (mean = 30.5 cm, SD = 1.6 cm), which was a 90% improvement from baseline measurements. In addition, forearm circumference was reduced (mean = 27.5 cm, SD = 2.4 cm). This was a 93% improvement from baseline measurements. There was a significant reduction in arm volume from pre- to post-treatment (p > 0.01).
Combining laser liposuction with lymph node flap transfer is a novel procedure. In this study, the intervention appeared safe and reliable, and it was an effective way to significantly reduce limb volume in patients with breast cancer experiencing upper limb lymphedema.
Free lymph node flap transfer and laser-assisted liposuction is very new for lymphedema treatment. This study's results were confusing, and nurses should continue observing this method. The small sample size makes it difficult to determine the extent to which this intervention would be effective for the majority of patients with upper limb lymphedema.
Nicolatou-Galitis, O., Sarri, T., Bowen, J., Di Palma, M., Kouloulias, V.E., Niscola, P., . . . Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO). (2013). Systematic review of anti-inflammatory agents for the management of oral mucositis in cancer patients. Supportive Care in Cancer , 21(11), 3179–3189.
PURPOSE: Systematically review literature and define updated clinical practice guidelines regarding use of anti-inflammatory agents
TYPES OF PATIENTS ADDRESSED: Patients receiving chemotherapy or radiation therapy
RESOURCE TYPE: Evidence-based guideline
PROCESS OF DEVELOPMENT: Studies evaluated using Hadorn criteria and assigned levels of evidence on Somerfield criteria by independent reviewers. Findings were integrated into guidelines based on overall level of evidence for each intervention.
DATABASES USED: MEDLINE (1966–December 31, 2010)
KEYWORDS: aminosalicylic acid, amifostine, amlexanox, anti-inflammatory, anti-TNF, anti-tumor necrosis factor, aspirin, Benadryl®, benzydamine, betamethasone, celecoxib, corticosteroid, dexamethasone, diphenhydramine, Ethyol®, flurbiprofen, histamine, hydrocortisone, ibuprofen, indomethacin, infliximab, irsogladine, lactoferrin, mesalazine, misoprostol, N-acetylcysteine, non-steroidal anti-inflammatory agents, NSAIDS, orgotein, prednisone, prostaglandin, RK-02-02, salicylic acid, steroid, thalidomide, TNF antibody, TNF inhibitor, and tumor necrosis factor/TNF
INCLUSION CRITERIA: Articles involving anti-inflammatory agents for prevention or treatment of oral mucositis
PHASE OF CARE: Active antitumor treatment
Forty-one studies were included in the review involving use of multiple anti-inflammatory agents.
Two new guidelines were identified by this systemic review. The panel suggests that misoprostol mouthwash should not be used for the prevention of radiation-induced oral mucositis in patients with head and neck cancer. The other new guideline the panel recommends is benzydamine mouthwash for the prevention of oral mucositis in patients with head and neck cancer receiving moderate-dose radiation therapy (up to 50 Gy) without concomitant chemotherapy. In addition to this, the lack of clear evidence supporting the use of any anti-inflammatory agent other than benzydamine, the use of anti-inflammatory agents continues to be a promising strategy for the prevention and treatment of oral mucositis. More well-designed studies are needed to examine the use of anti-inflammatory agents for oral mucositis in various cancer care settings.
Nicolatou-Galitis, O., Dardoufas, K., Markoulatos, P., Sotiropoulou-Lontou, A., Kyprianou, K., Kolitsi, G., … Velegraki, A. (2001). Oral pseudomembranous candidiasis, herpes simplex virus-1 infection, and oral mucositis in head and neck cancer patients receiving radiotherapy and granulocyte-macrophage colony-stimulating factor (GM-CSF) mouthwash. Journal of Oral Pathology and Medicine, 30, 471–480.
Patients were given a mouthwash of 400 mcg granulocyte-macrophage colony-stimulating factor (GM-CSF) dissolved in 1 mL sterile water, added to 200 mL drinking water, to treat grade II–IV mucositis. Patients were instructed to use the mouthwash once a day after the end of the second week of therapy. They were instructed to use as a mouthwash and then swallow in fragments within one hour.
Physicians used the following grading system.
Patients used the following grading system.
The authors stated that because 20 out of 46 patients with initial mucositis of grade II and III completed RT with grade I mucositis, the mouthwash was beneficial. However, additional research is needed.
Nicolatou-Galitis, O., Sarri, T., Bowen, J., Di Palma, M., Kouloulias, V.E., Niscola, P., . . . Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO). (2013). Systematic review of amifostine for the management of oral mucositis in cancer patients. Supportive Care in Cancer, 21(1), 357–364.
STUDY PURPOSE: To review available literature from 1966 to December 31, 2010 to define clinical practice guidelines for the use of amifostine for prevention and treatment of oral mucositis in patients with cancer
TYPE OF STUDY: Systematic review
DATABASES USED: MEDLINE
KEYWORDS: Extensive list provided (anti-inflammatory agents) including amifostine, antitumor necrosis factor (TNF), non-steroidal anti-inflammatory drugs, TNF inhibitor, etc.
INCLUSION CRITERIA: Detailed information is provided in a different section of the journal. Studies relevant to the management of radiation and/or chemotherapy-induced oral mucositis using anti-inflammatory interventions including amifostine
EXCLUSION CRITERIA: Articles that did not report on intervention and mucositis outcomes, animal or in vitro studies, non-English articles, methodologic quality, and anti-inflammatory agents other than amifostine
TOTAL REFERENCES RETRIEVED: 908
EVALUATION METHOD AND COMMENTS ON LITERATURE USED: Only articles that investigated amifostine specifically were selected. Levels of evidence were based on the Somerfield criteria, and study methodology was evaluated on the Hadorn criteria. These were integrated into guideline categories—recommendation, suggestion, or no guideline possible.
PHASE OF CARE: Active antitumor treatment
No guideline, suggestion, or recommendation for mucositis prevention with amifostine was possible in any of the following groupings.
Conflicting results, insufficient data, and major Hadorn flaws did not allow any guideline related to the use of amifostine for oral mucositis prevention. New well-designed trials are necessary that include timing of amifostine infusion prior to radiotherapy, consistent dose of amifostine, and cancer therapy intensity and modality.
Too many studies may have been eliminated up front.
Because no guidelines are recommended by this review, nurses who continue to administer amifostine for mucositis prevention carefully should document the results and look for ways to participate in well-designed trials. Nurses may consider advocating against the use of amifostine outside of research until guidelines can be established for its use.
Nicholson, A.B. (2006). Methadone for cancer pain [Cochrane review]. In The Cochrane Library, Volume 4, 2006. Oxford, UK: Update Software.
To determine the effectiveness and safety of methadone analgesia in patients with cancer pain; to assess the adverse effects associated with methadone analgesia for the treatment of cancer pain
Databases searched were Cochrane Pain, Palliative & Supportive Care Group Trials Register; The Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE; EMBASE; CancerLIT; CINAHL; National Research Register; CenterWatch clinical trials listing service; Current Controlled Trials; National Institutes of Health Clinical Trials Databases; BioMed; Glaxo Wellcome Clinical Trials Register; National electronic Library for Health (NeLH); System for Information on Grey Literature in Europe (SIGLE); Dissertation Abstracts OnDisc; Index to Theses (ASLIB Index); Proquest Digital Dissertations; Cochrane Database of Systematic Reviews (CDSR); and Database of Abstracts of Reviews of Effects (DARE).
Evidence suggests that methadone is an analgesic with an efficacy similar to that of morphine and with side effects that are similar to those of morphine. Although methadone is similar to morphine, the pharmacokinetics and pharmacodynamics of methadone make dose titration difficult. Methadone presents the risk of drug accumulation to toxic levels. There is a significant danger that the effect of methadone accumulation leading to delayed onset of adverse effects has not been represented. The majority of studies involved were single-dose comparisons or pertained to short-term use. Such comparisons fail to reproduce clinical practice; such studies do not reveal delayed adverse effects. One study, which compared methadone to morphine over 28 days, reported an increased rate of withdrawal from the methadone group. Withdrawal was due to side effects. Author drew no conclusion regarding the relative merits, in the management of various pain syndromes, of methadone compared to those of other opioids. The additional study found methadone to be as effective as morphine in the treatment of neuropathic pain, but not superior to morphine.
Few studies presented complete data sets regarding pain. No meta-analysis was possible.
Niazi, T. M., Vuong, T., Azoulay, L., Marijnen, C., Bujko, K., Nasr, E., . . . Cummings, B. (2012). Silver clear nylon dressing is effective in preventing radiation-induced dermatitis in patients with lower gastrointestinal cancer: results from a phase III study. International Journal of Radiation Oncology, Biology, Physics, 84, e305-e310.
To compare the efficacy of silver clear nylon dressing to standard skin care for the prevention and treatment of radiodermatitis in patients with anal canal and rectal cancer receiving chemoradiation therapy (XRT).
Patients were randomized to receive the silver dressing beginning on day 1 of radiation treatment or standard of care if radiation-induced dermatitis developed. Standard care involved using sulfadiazine cream at the time of development of grade 1 dermatitis. Patients wore the dressing 24 hours/day, seven days/week, except during XRT delivery. This was continued until two weeks after completion of XRT. The primary study outcome was skin toxicity at the last day of XRT. Skin toxicity was rated by multiple observers from digital photographs of the perineal skin area.
Patients were undergoing the active antitumor treatment phase of care.
Skin scoring system grade 0–4: grading by all 10 observers was calculated as the average score x10.
All patients completed XRT without major toxicity. There were four treatment breaks in the standard care arm and three in the silver dressing arm. On the last day of treatment, the mean dermatitis score was 2.53 for the standard arm and 1.67 for the silver dressing arm. When adjusted for age, there was no significant difference between groups in terms of severity of radiodermatitis.
There were no clear differences between study groups that indicated a substantial benefit for use of silver dressings.
*Dressings were provided free of charge; however, they are generally expensive. Measurement methods were unclear; the authors stated calculation of dermatitis severity using all 10 observer scores but then reported analysis only of average findings in each group. Findings showed no significant difference or meaningful size of effect; however, the authors concluded that the dressing was beneficial, which showed bias in the reporting.
The study did not provide strong support for the efficacy of silver nylon dressing to prevent radiation-induced dermatitis with radiation to the perineal area and skin.